3 INTRODUCTIONThe protein is found in normal urine, and it’s divided into:1-60% plasma proteins: albumin (major) IgG, IgA ,light chains ,heavy chains , transferrin ,haptoglobin ,lysozyme ,amylaze ,kallikrein.2- 40% originating from the secretions of the urinary tract including: tamm-horstall ,urokinase and secertory IgA.The reasonable upper limit of normal protien excretion in healthy children = 150 mg/24 hrs.
4 DEFINITIONThe excretion of an excessive amount of protein (>150mg/day) in the urine as defined by qualitative, semi-quantitative, and quantitative methods.
5 EPIDEMIOLOGYincidence: 1 - 5% (depend upon age and number of samples)prevalence: % (1+ proteinuria)only 10% of kids with proteinuria will have abnormalities after 6-10 month of follow-upof those children with isolated proteinuria, <2% will have significant underlying renal diseasethe incidence of proteinuria in patients with underlying renal disease is remarkably high
6 There are three basic types of proteinuria : PATHOGENESISThere are three basic types of proteinuria :1-glomerular2-tubular3- overflow
14 3. Overload Proteinuria 1. Neoplastic 2. Others Amyloidosis Leukemia (monocytic, monomyelocytic) - lysozymuriaMultiple MyelomaWaldenstrom's Macroglobinemia2. OthersIDDM (microalbuminuria)repeated albumin or blood transfusionsRhabdomyolysismost common causes of proteinuria in childhood
15 CLINICAL FEATURES: 1. History of Presenting Illness at the end of the history, one should be able to discern:1. benign vs pathologic proteinuria (if pathologic then)2. glomerular vs tubulointerstitial proteinuria (if glomerular then)3. hereditary vs non-hereditary (if non-hereditary then)4. acute GN vs chronic GN (if chronic then)5. primary GN vs secondary GN6. nephrotic vs non-nephrotic proteinuria7. proteinuria with or without hematuriauriaonsetwhen began with conditions identified around the initial presentation, i.e., drug ingestionrecord of previous urinalysesprecipitation/palliationidentification of triggering agentsinfectious, drugs, foods, chemicals, vaccinationshelps to identify acquired forms of tubulointerstitial proteinuria
16 associated with hematuria severity qualityassociated with hematuriaseveritymore likely to be pathologic proteinuria if associated with hematuria or Nephrotic Syndrome (edema, hypoalbuminemia, hypercholesterolemia)if Nephrotic Syndrome present:likely to be a primary GNunlikely to be benign etiology or secondary GNtimingacute vs acute-on-chronicintermittent vs persistentduration of proteinuriaassociated symptomspast medical historyfunctional inquiryhelps to differentiate acute GN from chronic GNhelps to identify overload proteinuria causes
17 Family Historyhelps to differentiate hereditary from non-hereditary forms of both glomerular and tubulointerstitial forms of proteinuria:1. Proteinuriafamily members must have had previous urinalysis to ascertain this2. Renal DiseasePolycystic Kidney DiseaseNephrotic Syndrome, Fanconi Diseaserenal dialysiskidney transplantation3. Othershearing/ocular impairment (Alport Syndrome)
18 Specific Entities 1. Benign Transient Proteinuria benign proteinuria associated with precipitating factors - fever, exercise, stress, cold weather, dehydration, high blood pressure, seizures, etcOrthostatic Proteinuria2.diagnosis based upon the Postural Testhas a benign clinical course
19 3. Persistent Asymptomatic Proteinuria proteinuria that persists for 3-6 monthsrenal biopsy after 6 months of persistent proteinuria and if FSGS then at risk for chronic renal failure4. Congenital Nephrotic Syndromeonset at birth with Nephrotic Syndrome (massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia)very difficult to treat with poor prognosis5. Poststreptococcal GNproteinuria + hematuriaassociated symptomsprodrome of pharyngitis, URTI, impetigoNephrotic and/or Nephritic Syndrome
21 9. Secondary Glomerulonephritis proteinuria +/- hematuria associated with a disease entity, i.e., SLE, Goodpastures Disease, Wegeners Disease, Diabetes Mellitus10. Hereditary Tubulointerstitial Proteinuriastubular proteinuriaassociated symptomsepisodes of vomiting, dehydration, weakness, fever, anorexia, constipation, failure to thrive, polydipsia, polyuria
22 INVESTIGATIONS 1. Proteinuria (Diagnosis) 1. Qualitative - Dipstick measures a range of protein concentrationsdepth of colour increases in a semiquantitative manner with increasing urinary protein concentrationto rule out false positives must have:3 samples with proteinuriafirst voided early morning samplespH < 6.0 with known specific gravity1+ ( mg/24 hrs) or greater is considered abnormaldependent on specific gravity of urine sampleFP: gross hematuria, highly alkaline urine, UTI
23 2. Semi-quantitative - Protein/Creatinine Ratio in Urine random early morning single voided specimenchildren < 2 years : < 0.5children > 2 years : < 0.2nephrotic : > 3.5correlates with the 24 hour protein excretion data
24 3. Quantitative - 24 hr. urine collection gold standardif dipstick is 1+ or more than obliged to do a 24 hour urine collection24 hr. urine collectionProtein (mg)/m2/hr< 4 mg/m2/hourr (normal)4-40mg/m2/hour (proteinuria)40 mg/m2/hour (nephrotic)Protein (mg)/24 hr2 to 12 months : > 155 mg/24 hr3 to 4 years : > 140 mg/24 hr4 to 10 years : > 190 mg/24 hr10 to 16 years : > 250 mg/24 hrFP: radiographic contrast media, cephalosporins, pencillin analogues, sulfonamide metabolites
25 2. Indications for Further Investigation Non-orthostatic ProteinuriaPersistent ProteinuriaSymptomatic (edema, elevated BP, abdominal pain, hematuria)
26 3. First Line Investigations 1. UrinalysisR&M, C&S, microscopyorthostatic test24 hour collectiontotal proteincreatinine clearance2. Serumelectrolytes, BUN, creatinine, albumin, cholesterol, triglyceride, calcium, protein, CBC4. Second Line Investigations1. Urineprotein electrophoresis can be used to differentiate glomerular (albumin) from tubular (Tamm-Horstall) proteinuria2. SerumIgA, PTH, ANA, protein electrophoresis, ASOT, anti-GBM antibodies, uric acid, C3, C43. Imaging Studiesrenal ultrasound to rule out renal vein thrombosis4. Renal Biopsyindicated for:progressive proteinuria with hematuriaall forms of Nephrotic Syndrome except that caused by steroid-responsive Minimal Change Disease